Syndecan-4在斑马鱼心脏再生的早期修复反应中是必需的。

Syndecan-4 is required for early-stage repair responses during zebrafish heart regeneration.

作者信息

Lai Zih-Yin, Yang Chung-Chi, Chen Po-Hsun, Chen Wei-Chen, Lai Ting-Yu, Lu Guan-Yun, Yang Chiao-Yu, Wang Ko-Ying, Liu Wei-Cen, Chen Yu-Chieh, Liu Lawrence Yu-Min, Chuang Yung-Jen

机构信息

School of Medicine, National Tsing Hua University, Hsinchu, 300044, Taiwan, ROC.

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 300044, Taiwan, ROC.

出版信息

Mol Biol Rep. 2024 May 3;51(1):604. doi: 10.1007/s11033-024-09531-4.

DOI:10.1007/s11033-024-09531-4

PMID:38700644

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11068835/

Abstract

BACKGROUND

The healing process after a myocardial infarction (MI) in humans involves complex events that replace damaged tissue with a fibrotic scar. The affected cardiac tissue may lose its function permanently. In contrast, zebrafish display a remarkable capacity for scar-free heart regeneration. Previous studies have revealed that syndecan-4 (SDC4) regulates inflammatory response and fibroblast activity following cardiac injury in higher vertebrates. However, whether and how Sdc4 regulates heart regeneration in highly regenerative zebrafish remains unknown.

METHODS AND RESULTS

This study showed that sdc4 expression was differentially regulated during zebrafish heart regeneration by transcriptional analysis. Specifically, sdc4 expression increased rapidly and transiently in the early regeneration phase upon ventricular cryoinjury. Moreover, the knockdown of sdc4 led to a significant reduction in extracellular matrix protein deposition, immune cell accumulation, and cell proliferation at the lesion site. The expression of tgfb1a and col1a1a, as well as the protein expression of Fibronectin, were all down-regulated under sdc4 knockdown. In addition, we verified that sdc4 expression was required for cardiac repair in zebrafish via in vivo electrocardiogram analysis. Loss of sdc4 expression caused an apparent pathological Q wave and ST elevation, which are signs of human MI patients.

CONCLUSIONS

Our findings support that Sdc4 is required to mediate pleiotropic repair responses in the early stage of zebrafish heart regeneration.

摘要

背景

人类心肌梗死（MI）后的愈合过程涉及复杂事件，即受损组织被纤维化瘢痕替代。受影响的心脏组织可能会永久丧失其功能。相比之下，斑马鱼显示出显著的无瘢痕心脏再生能力。先前的研究表明，syndecan - 4（SDC4）在高等脊椎动物心脏损伤后调节炎症反应和成纤维细胞活性。然而，Sdc4是否以及如何调节高再生能力斑马鱼的心脏再生仍不清楚。

方法与结果

本研究通过转录分析表明，sdc4在斑马鱼心脏再生过程中表达受到差异调节。具体而言，在心室冷冻损伤后的早期再生阶段，sdc4表达迅速且短暂增加。此外，敲低sdc4导致病变部位细胞外基质蛋白沉积、免疫细胞积聚和细胞增殖显著减少。在敲低sdc4的情况下，tgfb1a和col1a1a的表达以及纤连蛋白的蛋白表达均下调。此外，我们通过体内心电图分析证实，sdc4表达是斑马鱼心脏修复所必需的。sdc4表达缺失导致明显的病理性Q波和ST段抬高，这是人类MI患者的体征。